Total Synthesis of Petrobactin and Its Homologues as Potential Growth Stimuli for Marinobacter hydrocarbonoclasticus, an Oil-Degrading Bacteria

A modular synthesis was developed to access petrobactin, a catechol-containing siderophore isolated from Marinobacter hydrocarbonoclasticus. A range of petrobactin homologues with differing dihydroxybenzamide motifs and in one case an increased number of carbons in the polyamine backbone were also synthesized. As such, these systems represent new isomeric probes to study iron transport properties in M. hydrocarbonoclasticus. The synthesis of petrobactin and its homologues and the first biological study of how these agents influence the growth of Mycobacterhydrocarbonoclasticus are reported. New synthetic methods were developed to overcome issues (imide formation) encountered in earlier syntheses. Both the (1)H and (13)C NMR of petrobactin were consistent with the recently revised structure showing that petrobactin in fact contains a 3,4-dihydroxybenzene motif rather than a 2,3-dihydroxybenzene motif. The preliminary biological studies suggested that using the native petrobactin 1b for M. hydrocarbonoclasticus-specific growth stimulation may be a poor strategy for oil-spill cleanup.